The E3 ligase MuRF2 plays a key role in the functional capacity of skeletal muscle fibroblasts.

Fibroblasts are a highly heterogeneous population of cells, being found in a large number of different tissues. These cells produce the extracellular matrix, which is essential to preserve structural integrity of connective tissues. Fibroblasts are frequently engaged in migration and remodeling, exerting traction forces in the extracellular matrix, which is crucial for matrix deposition and wound healing. In addition, previous studies performed on primary myoblasts suggest that the E3 ligase MuRF2 might function as a cytoskeleton adaptor. Here, we hypothesized that MuRF2 also plays a functional role in skeletal muscle fibroblasts. We found that skeletal muscle fibroblasts express MuRF2 and its siRNA knock-down promoted decreased fibroblast migration, cell border accumulation of polymerized actin, and down-regulation of the phospho-Akt expression. Our results indicated that MuRF2 was necessary to maintain the actin cytoskeleton functionality in skeletal muscle fibroblasts via Akt activity and exerted an important role in extracellular matrix remodeling in the skeletal muscle tissue.

The E3 ligase MuRF2 plays a key role in the functional capacity of skeletal muscle fibroblasts

Fibroblasts are a highly heterogeneous population of cells, being found in a large number of different tissues. These cells produce the extracellular matrix, which is essential to preserve structural integrity of connective tissues. Fibroblasts are frequently engaged in migration and remodeling, exerting traction forces in the extracellular matrix, which is crucial for matrix deposition and wound healing. In addition, previous studies performed on primary myoblasts suggest that the E3 ligase MuRF2 might function as a cytoskeleton adaptor. Here, we hypothesized that MuRF2 also plays a functional role in skeletal muscle fibroblasts. We found that skeletal muscle fibroblasts express MuRF2 and its siRNA knock-down promoted decreased fibroblast migration, cell border accumulation of polymerized actin, and down-regulation of the phospho-Akt expression. Our results indicated that MuRF2 was necessary to maintain the actin cytoskeleton functionality in skeletal muscle fibroblasts via Akt activity and exerted an important role in extracellular matrix remodeling in the skeletal muscle tissue.

Thyroid hormone upregulates MDM2 in rat type I fibre: Implications for skeletal muscle mass regulation.

AIM: Based upon a microarray assay, we have identified that triiodothyronine (T3) upregulates MDM2 gene expression in the rat skeletal muscle. As MDM2 protein is an E3 ligase, we hypothesized that this enzyme could play a role in T3 effects on skeletal muscle mass control. METHODS: To test our hypothesis, male rats (2 months old) were randomly assigned into the following groups: intact controls, treated with 20 physiological doses of T3 for 0.5, 1 and 7 days, or with 5, 20 and 50 physiological doses of T3 for 7 days. For in vitro experiments, myotubes and C2C12 cells were treated with T3 for 3 days. RESULTS: After validation of the microarray finding throughout RT-PCR and confirmation that T3 induces increases in MDM2 protein expression in a dose-dependent manner, we observed that MDM2 was upregulated by T3 exclusively in fibre type I. Moreover, detailed histological evaluation showed that MDM2 overexpression distributes punctiformily along the cross section of the fibre and also inside nuclei. MDM2 colocalizes with PAX7 in control muscle and T3 downregulates this myogenic factor. Pharmacological inhibition of MDM2 in cultured myotubes caused a severe decrease in their diameter (~35%, P < .001 vs Control), enhancing the effect of T3 (from ~12% to ~35%, P < .001) alone upon myotube diameter and mRNA levels of atrogenes. Finally, we observed that FOXO3 (MDM2 target) is kept outside the nucleus under T3 stimulation. CONCLUSION: Our results indicate that MDM2 might be involved in the pro-trophic effects of T3 in skeletal muscle.

Antibacterial activity of the essential oil from Lippia aff. gracillis.

The essential oil of fresh leaves of Lippia aff. gracillis was analyzed by GC/MS and evaluated for its antibacterial effects. The results showed a moderate antibacterial activity and confirm the traditional uses of L. aff. gracillis.

Relevance of apoptosis and cell proliferation for survival of patients with dilated cardiomyopathy undergoing partial left ventriculectomy.

BACKGROUND: Cardiomyocyte apoptosis as well as proliferation have been described in congestive heart failure, but their clinical relevance remains unclear. In order to clarify whether apoptosis and cell proliferation occur in patients with idiopathic dilated cardiomyopathy and whether their degree in left ventricle fragments resected during partial left ventriculectomy has any influence on the outcome after this surgery, we compared their occurrence in four groups of patients: group A, short-term survivors (n = 18); group B, deaths within 6 months of the surgery (n = 13); group C, long-term survivors (n = 12); and Group D, deaths within 60 months (n = 19). DESIGN: Apoptotic cardiomyocytes and interstitial cells were quantified in left ventricle fragments from 31 patients with idiopathic-dilated cardiomyopathy using the TUNEL assay. Cell proliferation was quantified in parallel sections by KI-67 immunohistochemistry. RESULTS: Apoptotic cells were present in the majority of cases (n = 24) and proliferative cells in all cases. Whereas there was no significant difference regarding all parameters examined between Groups A and B, there was a highly significant difference between Groups C and D in the number of apoptotic cardiomyocytes (P = 0.012) and apoptotic interstitial cells (P = 0.006). There was no significant relationship between apoptotic cardiomyocytes and KI-67-positive cardiomyocytes, but a negative correlation between apoptotic interstitial cells and KI-67-positive interstitial cells (r = -0.383; P = 0.028). CONCLUSION: Cardiomyocyte apoptosis and proliferation occur in the majority of patients with idiopathic-dilated cardiomyopathy. High numbers of apoptotic cardiomyocytes and apoptotic interstitial cells are significantly related to a bad late outcome after partial left ventriculectomy.

Atheromas that cause fatal thrombosis are usually large and frequently accompanied by vessel enlargement.

Several lines of clinical evidence show that AMI frequently occurs at sites with mild to moderate degree of coronary stenosis. The degree of luminal stenosis depends on plaque deposition and degree of vessel remodeling, features poorly assessed by coronary angiography. This postmortem study tested the hypothesis that the size of coronary atheroma and the type of remodeling distinguish culprit lesion responsible for fatal AMI from equi-stenotic nonculprit lesion in the same coronary tree. The main coronary branches from 36 consecutive patients with fatal AMI were studied. The culprit lesion (Group 1) and an equi-stenotic nonculprit segment (Group 2) obtained in measurements of another coronary branch from the same patient were compared. Morphometry and plaque composition was assessed in both groups. Compared to Group 2, Group 1 had larger areas of: plaque 9.6 vs. 4.7 mm(2), vessel 12.7 vs. 7.4 mm(2) and lumen 1.7 vs. 1.2 mm(2); (P< .01). Positive remodeling was more frequent in Group 1 than Group 2: 21/30 (70%) vs. 8/26 (31%). Plaque area correlated positively with lipid core and macrophages and negatively with fibrosis and smooth muscle cells. Atherosclerotic plaques that cause fatal thrombosis are more frequently positively remodeled and tend to be larger than nonculprit plaques with the same degree of cross-sectional stenosis. We tested whether arterial remodeling and plaque size vary between segments containing a fatal thrombosed plaque versus an equi-stenotic nonculprit plaque. Culprit vessel segments had higher cross-sectional areas of intimal plaque and of vessel wall than equi-stenotic nonculprit plaques. The cross-sectional area of the vessel correlated positively with both the lipid core area and CD68(+) macrophage content, and negatively with fibrosis area and smooth muscle cell content. These results add elements explaining limitations of angiography in identifying plaques and provide new insights into the role of remodeling in plaque instability.

Embolia pulmonar en autopsias de drogadictos / Pulmonary embolism in autopsies of drug abusers

Antecedentes: Pocos estudios de autopsia han investigado la presencia de embolia pulmonar en drogadictos.Objetivo: Determinar en autopsias de drogadictos la presencia de embolia pulmonar.Diseño: Estudio retrospectivo de 1228 autopsias realizadas en el año de 1999. Lugar del estudio: Servicio Médico Forense de Tijuana, BC. México. Material y métodos: De 71 casos de embolia pulmonar identificados en 1999, 20 fueron seleccionados para estudio con base en haber tenido embolia pulmonar, pruebas toxicológicas en la sangre positivas y sin otra causa aparente de muerte. La embolia se identificó al abrir la arteria pulmonar; se realizaron pruebas de laboratorio toxicológicas en sangre para determinar opio y derivados (cocaína, heroína) y metanfetaminas; también se determinaron niveles de alcohol en la sangre y se registró la presencia de signos de flebitis superficial o venopunción y de tatuajes en la piel. Resultados: Se encontraron 20 sujetos: 19 del sexo masculino y uno del sexo femenino. La edad media fue de 32 años. Tuvieron resultados positivos en sangre para opio y sus derivados 18 casos, para anfetaminas dos y para alcohol 17. Se encontraron diversos tatuajes en 16 y existía evidencia de venopunción o flebitis superficial en 12 casos. Conclusiones: En 1228 autopsias realizadas en el Servicio Médico Forense de Tijuana, BC. en 1999, se encontraron 71 casos de embolia pulmonar, de los cuales 20 (28 por ciento) tuvieron evidencia de drogadicción y consumo de alcohol. Se conoce poco respecto al efecto de drogas, como la cocaína, en el proceso de la coagulación, pero de modo experimental aumenta la agregación plaquetaria y la producción de tromboxano.

Myocardial fiber diameter as a good indicator of outcome in Batista's operation.

BACKGROUND: Despite the initial promissory results of partial left ventriculectomy, or Batista's operation, the postoperative mortality associated with the procedure has been too high. We described a histopathologic study performed to identify histological parameters that could help to determine outcomes of patients undergoing this procedure. METHODS AND RESULTS: Myocardial fiber diameter, myocardial fibrosis, thickness of the compact wall, and number of cells presenting from the endocardium to epicardium were analyzed in 32 patients with idiopathic dilated cardiomyopathy who underwent Batista's operation. Data were grouped by patients who died < or = 6 months and patients who survived for > 6 months after the surgical procedure. Additional analyses were performed to compare results according the causes of death and to test the application of these results to biopsy. RESULTS: Myocardial fiber diameter was the only index that could distinguish the two groups. Myocardial fiber diameter < 22 microm distinguished the group of patients who survived the 6-month postoperative period from patients who died during that time with sensitivity of 85.7 and specificity of 72.2. The subendocardial region of the compact wall and the trabecular portion of the wall exhibited comparable results. CONCLUSION: Our results indicate that the myocardial fiber diameter of samples from the trabecular or subendocardial compact wall regions may help predict the outcome of left ventriculectomy. Samples from the trabecular or subendocardial compact wall regions were used for analysis. Further prospective studies involving left ventricular endomyocardial biopsies are necessary to confirm if the use of myocardial fiber diameter in the selection of patients for surgery improves the index of success of Batista's operation. Other factors that are involved remain unclear.

Prevalência de doença oclusiva na bifurcaçäo carotídea em pacientes portadores de aterosclerose periférica / Prevalence of carotid lesion in patients with perpheral atherosclerosis

A aterosclerose é uma doença que produz lesöes em diversas localizaçöes nas artérias centrais e periféricas. Essas lesöes ocorrem algumas vezes de forma concomitante, produzindo insuficiência arterial nos territórios irrigados pelas artérias comprometidas. O presente estudo tem por finalidade demonstrar a frequência de lesöes ateroscleróticas em território carotídeo em pacientes portadores de insuficiência arterial periférica (IAPC) de causa aterosclerótica. Foram examinados através de Duplex Ultraom 68 pacientes (136 bifurcaçòes carotídeas). As lesöes foram classificadas em severas (estenoses com 80 por cento ou mais de reduçäo em diâmetro da artéria), moderadas (estenose com 50 a 80 por cento de reduçäo do diâmetro arterial) ou mínimas (estenoses com reduçäo de diâmetro menor que 50 por cento) de acordo com os critérios padronizados. Os resultados foram corralcionados com angiografia digital. A correlaçäo entre os exames Duplex e a angografia apresentou sensibilidade de 90 por cento e especificdde de 100 por cento. Encontramos 7,35 por cento de pacientes portadores de lesöes severas e 16,17 por cento com lesöes moderadas. Tem sido claramente demonstrado na literatura que estas säo as lesöes que potencialmente podem causar ataques isquêmicos transitórios (AIT), acidentes vasculares cerebrais isquêmicos (AVCIs) e amaurose fugax. Tendo-se em vista a morbidade das lesöes que potencialmente podem causar ataques isquêmicos transitórios (AIT), acidentes vasculares cerebrais isquêmicos (AVCIs) e amaroe fugax. Tendo-se me vista a morbidade das lesöes em território de artérias carótidas e a frequência destas em nosso grupo de pacientes (23,52 por cento do total), recomenda-se o exame Duplex como rotina propedêutica neste grupo de pacientes.

Ataque de nervios and panic disorder.

OBJECTIVE: Ataque de nervios ("attack of nerves") is an illness category used frequently by Hispanic individuals to describe one or more particular symptom complexes. A review of the literature on ataque suggested some overlap with panic disorder. This study investigated the overlap with panic disorder as well as other DSM-III-R axis I disorders. METHOD: Hispanic subjects seeking treatment at an anxiety disorders clinic (N = 156) were assessed with a specially designed questionnaire for self-report of ataque de nervios and panic symptoms and with structured or semistructured psychiatric interviews for axis I disorders. RESULTS: Seventy percent of the subjects reported at least one ataque de nervios; 80% of these were female, whereas 57% of the group without these attacks were female. There were no differences in DSM-III-R diagnoses between the groups with and without ataque de nervios. Ataque was frequently associated with one or more anxiety and affective disorders, including panic disorder, generalized anxiety disorder, recurrent major depression, and anxiety not otherwise specified. Of the 45 subjects with both ataque de nervios and primary panic disorder, 80% appeared to have labeled panic disorder as ataque. Ataque de nervios was associated with panic symptoms even in subjects without panic disorder, but the self-reporting of ataque conveyed additional clinical information about the subjects with panic disorder. Ataque de nervios was similar in frequency and symptoms among subjects of Dominican and Puerto Rican origin. CONCLUSIONS: Ataque de nervios overlaps with panic disorder but is a more inclusive construct. Further study of its interrelation with axis I disorders is needed.

Thin-section and freeze-fracture study of post-mortem changes in dog myocardium.

1. Fragments of dog hearts submitted to 1, 6, 10, 24 and 48 h of autolysis at 20 degrees C were studied with freeze-fracture and thin-section techniques under the transmission electron microscope. 2. The freeze-fracture replicas revealed maximal reduction in the mean number and clustering of intramembrane particles at 6 h post mortem, indicating irreversible cellular damage. However, signs of lethal damage (intramitochondrial amorphous dense bodies) were not observed in thin sections of the same material. 3. The present study indicates that signs of irreversible damage similar to that occurring in in vivo ischemic alterations can be detected earlier by the freeze-fracture technique than by the thin-section technique.

Thin-section and freeze-fracture study of post-mortem chenges in dog myocardium

Fragments of dog hearts submitted to 1,6,10,24 and 48 h of autolysis at 20-C were studied with freeze-fracture and thin-section techniques under the transmission electron microscope. The freeze-fracture replicas revealed maximal reduction in the mean number and clustering of intramembrane particles at 6 h post mortem, indicating irreversible cellular damage. However, sings of lethal damage (intramitochondrial amorphous dense bodies) were not observed in thin sections of the same material. The present study indicates that signs of irreversible damage similar to that occuring in in vivo ischemic alterations can be detected earlier by the freeze-fracture technique than by the thin-section technique

Infarto cerebral en pacientes menores de 50 anos. / Cerebral infarction in patients under 50 years old

Se informan los casos de 20 pacientes menores de 50 anos, de uno y otro sexo que presentaron una enfermedad vasculoencefalica isquemica. Este estudio abarca los anos 1979, 1980 y 1981. Existe un predominio del sexo masculino, pero sin ser significativa la diferencia. Los factores de riesgo mas evidentes en ambos sexos y los distintos grupos de edad fueron: la hipertension arterial y el habito de fumar. En los pacientes del sexo masculino se encontraron tres con el antecedente de la ingestion de bebidas alcoholicas. Ello se ha valorado como un factor de riesgo. Un paciente de nuestra serie tenia el antecedente de la ingestion de anticonceptivos.Fue aplicado el test de "t" para muestras pequenas